Patients with double-hit lymphoma (DHL), which is characterized by rearrangements of MYC and either BCL2 or BCL6, face poor prognoses. We conducted a retrospective multicenter study of the impact of baseline clinical factors, induction therapy, and stem cell transplant (SCT) on the outcomes of 311 patients with previously untreated DHL. At median follow-up of 23 months, the median progression-free survival (PFS) and overall survival (OS) rates among all patients were 10.9 and 21.9 months, respectively. Forty percent of patients remain disease-free and 49% remain alive at 2 years. Intensive induction was associated with improved PFS, but not OS, and SCT was not associated with improved OS among patients achieving first complete remission (P = .14). By multivariate analysis, advanced stage, central nervous system involvement, leukocytosis, and LDH >3 times the upper limit of normal were associated with higher risk of death. Correcting for these, intensive induction was associated with improved OS. We developed a novel risk score for DHL, which divides patients into high-, intermediate-, and low-risk groups. In conclusion, a subset of DHL patients may be cured, and some patients may benefit from intensive induction. Further investigations into the roles of SCT and novel agents are needed.

Current prognostic models for peripheral T-cell lymphoma (PTCL) have multiple limitations, and questions exist regarding applicability to current patients. We utilized the Surveillance Epidemiology and End Results (SEER)-18 database to evaluate factors affecting overall survival (OS) of PTCL in the modern era and identified 8802 patients between 2000-2010. Most subtypes of PTCL increased in incidence during the study period. In univariate analyses, age >55 years, black race, advanced stage, absence of extra-nodal disease, omission of radiation therapy (RT) and high-risk histology each predicted inferior OS (P 1·5 (P ? 0·0001) for death. Further, age ?55 years, black race and advanced stage maintained their significance in the MVA (P

The impact of race/ethnicity and the additional factors of age, sex, and socioeconomic status (SES) on follicular lymphoma (FL) outcomes have not been comprehensively studied and are not well defined. We examined population-based FL data from >18,000 patients in SEER-13 (1992-2009) investigating race/ethnicity and the impact of relevant factors including sex, age, and SES. Further, we compared data over two consecutive periods: Era-1 (1992-2000, n = 8,355) and Era-2 (2001-2009, n = 10,475). We identified 18,830 FL patients (White: n = 15,116; Hispanic: n = 1,627; Asian/Pacific Islander (A/PI): n = 1,002; and Black: n = 846). Median ages (years) differed significantly by race/ethnicity: White: 62.1, Hispanic: 57.3, A/PI: 60.7, and Black: 56.8 (P < 0.01 each race versus White). Overall survival (OS) was superior in Era-2 versus Era-1 for all patients (5-year: 76.7% versus 67.4%, respectively, P < 0.001). Further, survival was significantly improved for all age groups <80 years, for males (P = 0.0019), and females (P < 0.001) across eras. Females had superior OS compared with males in Era-1 (P = 0.004), but not in Era-2. Additionally, all races, except A/PI, had improved 5-year OS rates from Era-1 to Era-2. Finally, OS improved across eras for lower and higher SES populations; however those with higher SES were superior to lower SES patients in both eras. In conclusion, and in the largest comprehensive evaluation of US-based FL patients to date, we show that despite improvements in OS for FL over time, critical disparities across races/ethnicities, sex, and age groups remain in the modern era and warrant further studies.

The prognostic significance of extra-medullary chronic lymphocytic leukemia (EM-CLL) is unknown. We conducted a Medline database systematic search analyzing English language articles published between 1975 and 2012 identifying 192 cases. Patients with EM-CLL were more commonly treated than not (p

Diffuse large B-cell non-Hodgkin lymphoma (DLBCL) is a disease of the elderly, but our current guidelines and treatment paradigms for this disease are based on studies that have mainly enrolled younger patients. Because the number of people living beyond the age of 80 increased by more than 250% between 1960 and 2000, and since it is expected that the population over the age of 75 will triple by 2030, understanding how these elderly patients should be treated is paramount to improving outcomes for this potentially curable lymphoma. In this review, we outline the scope of the problem; we define "the elderly" and identify challenges in assessing this patient population. We also summarize pivotal studies that have been conducted in these elderly patients and suggest an algorithm to aid clinicians in making treatment decisions when faced with DLBCL patients older than 80.

The advent of rituximab, a chimeric monoclonal antibody against CD20, has arguably improved and changed the natural history of non-Hodgkin lymphoma and has become an essential component of front-line and relapsed disease treatment strategies. Given its tolerability and long half-life, rituximab has been investigated in the maintenance setting in follicular lymphoma. Several landmark studies have demonstrated improvement in progression-free survival in patients receiving maintenance rituximab compared to those observed. These favorable results were witnessed in front-line and in the relapsed setting using a variety of induction programs such as rituximab monotherapy or chemoimmunotherapy. Importantly, toxicities were predictable and manageable. Despite these encouraging results, many vital and practical questions remain unanswered. In this review, we critically analyze the data that led to the widespread use of maintenance rituximab in follicular lymphoma and attempt to answer the most important questions facing practicing oncologists when deciding on using this approach in their patients.

Erlotinib is active in patients with lung cancer; especially those who demonstrate a mutation in exons 18-21 in the epidermal growth factor receptor (EGFR) gene. Patients with lung cancer and brain metastases have poor prognosis as systemic chemotherapy is ineffective in treating the central nervous system (CNS) metastases due to its inability to cross the blood brain barrier. Herein, we report a case of a 61 year old female who presented with stage IV adenocarcinoma of the lung with bilateral cerebral and cerebellar CNS involvement. The patients tumor harbored a mutation in exon 19 in the EGFR gene. Treatment with erlotinib was started as soon as the molecular studies were available with remarkable and complete radiographic response in the CNS disease, and complete resolution of the previously detected metastases. The patient did not receive any other CNS intervention and radiation was not given due to the lack of CNS symptoms.

Cytogenetics play a major role in determining the prognosis of patients with acute myelogenous leukemia (AML). However, existing cytogenetics classifications were developed in chemotherapy-treated patients and might not be optimal for patients undergoing allogeneic hematopoietic cell transplantation (HCT). We studied 821 adult patients reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) who underwent HCT for AML in first or second complete remission between 1999 and 2004. We compared the ability of the 6 existing classifications to stratify patients by overall survival. We then defined a new scheme specifically applicable to patients undergoing HCT using this patient cohort. Under this scheme, inv(16) is favorable, a complex karyotype (4 or more abnormalities) is adverse, and all other classified abnormalities are intermediate in predicting survival after HCT (5-year overall survival, 64%, 18%, and 50%, respectively; P = .0001). This scheme stratifies patients into 3 groups with similar nonrelapse mortality, but significantly different incidences of relapse, overall and leukemia-free survival. It applies to patients regardless of disease status (first or second complete remission), donor type (matched related or unrelated), or conditioning intensity (myeloablative or reduced intensity). This transplantation-specific classification could be adopted for prognostication purposes and to stratify patients with AML and karyotypic abnormalities entering HCT clinical trials.

To evaluate the efficacy and toxicity of the combination of VRCD (velcade/rituximab/cyclophosphamide/dexamethasone) in chemotherapy-naïve low-grade non-Hodgkin lymphoma or patients with transplantation-ineligible mantle cells.

The treatment of chronic lymphocytic leukemia (CLL) has evolved over the past decade. Our better understanding of disease biology and risk stratification has allowed delivering more effective therapies. In fact, front-line chemoimmunotherapy has demonstrated improvement in overall survival when compared to chemotherapy in randomized studies. Yet, treatment of relapsed CLL remains challenging and few agents are effective in that setting. Ofatumumab (Ofa) is a humanized monoclonal antibody targeted against CD20 with demonstrable activity in rituximab-resistant CLL cell lines. This agent was recently approved for the treatment of relapsed/refractory CLL patients who have failed fludarabine and alemtuzumab. In this review, we provide a historical perspective on approaches to CLL as front-line and in the relapsed setting. We further summarize novel anti-CD20 antibodies with specific emphasis on ofa. We review studies that led to ofatumumabs approval including pre-clinical data, trials using ofa in combination therapies, and adverse events/toxicities reported with this agent.

The previous decade has witnessed remarkable advances in our understanding and treatment of chronic lymphocytic leukemia. Chemoimmunotherapy has provided patients with unprecedented remission rates and has improved survival compared to chemotherapy alone. However, the availability of targeted therapies and monoclonal antibodies argues for exploring non-cytotoxic and biologic regimens for this disease. In this article, we review available targeted and non-chemotherapeutic agents for CLL, attempting to position these therapies in the treatment paradigm of CLL in the era of risk stratification as we move forward.

Currently, no standard therapy exists for patients with relapsed and/or refractory non-Hodgkin lymphoma (NHL) who are ineligible for transplantation or who have failed after bone marrow transplantation. The authors of this report investigated the safety and efficacy of clofarabine (CLO) in these patients.

A 63-year-old man with castrate-resistant metastatic prostate adenocarcinoma with known osseous and pelvic nodal involvement presented with progressive dyspnea for one week. Complete cardiopulmonary evaluation revealed a restrictive lung defect that could not be attributed to any of his previous therapies. On presentation, physical examination revealed coarse breath sounds diffusely with hypoxemia. Computed tomography of the chest showed severe bilateral airspace opacities and ground-glass appearance most consistent with interstitial pneumonitis. The patient was intubated due to progressive hypoxemia and worsening respiratory status despite empiric antibiotics and high dose steroids. Subsequent emergent bronchoscopy with transbronchial biopsies revealed atypical intralymphatic cells that stained positively for prostate-specific antigen and prostatic-specific acid phosphatase, confirming the diagnosis of intralymphatic pulmonary metastasis from prostate adenocarcinoma. Lymphangitic pulmonary metastasis from prostate adenocarcinoma is exceedingly rare, with few reported cases that are biopsy-proven. Herein, we describe a rare case of biopsy-proven lymphangitic pulmonary metastasis in the setting of castrate-resistant prostate adenocarcinoma and provide a comprehensive literature review.

Recent insights into mechanisms by which prostate cancer becomes castration resistant have allowed better and more rational therapeutic design. These novel therapies have complemented the modest success that chemotherapy has shown in recent years changing the landscape of this disease and leading to improved outcomes. Angiogenesis and immune deregulation are 2 pathways that have increasingly been shown to lead into castration resistant prostate cancer (CRPC). Thalidmide and lenalidomide are immunomodulatory agents with antiangiogenesis properties that have shown activity in this setting with acceptable safety profile. In this review, we discuss briefly the different mechanisms that render prostate cancer castration resistant and elaborate on thalidomide and lenalidomide data in CRPC after reviewing their theoretic mechanisms of action. This timely review coincides with the identification of newer therapies against CRPC affirming our steady movement toward better disease control.

While rituximab-based chemo-immunotherapy has improved response and long-term survival rates in diffuse large B-cell non-Hodgkin lymphoma (DLBCL), relapse and death from recurrent disease is still the eventual outcome in a significant proportion of patients, especially those with high-risk disease. Autologous hematopoietic stem cell transplant (AHSCT) in first remission, which was studied mainly before the advent of rituximab, has lost its appeal due to several small negative trials. However, definitive data do not exist to determine the role of AHSCT in first remission. In this review, we critically evaluate studies investigating AHSCT in DLBCL in first remission. Most available studies have shortcomings that limit the applicability of their findings. AHSCT in first remission may have a role in selected patients with high-risk DLBCL, but a carefully designed prospective study is required to appropriately evaluate this concept.

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

How does it work?

We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.